The aim of this research is to look at two conditions, Essential Thrombocythemia (ET) and Polycythemia Vera (PV). ET causes people to produce too many blood cells called platelets and PV causes too many platelets and red blood cells to be made. Platelets are particles which circulate in the blood stream and normally prevent bleeding and bruising. Having too many platelets in the blood increases the risk of developing blood clots, which can result in life threatening events like heart attacks and strokes. When the number of red blood cells is increased in PV this will slow the speed of blood flow in the body and increases the risk of developing blood clots.

It is important for patients with ET or PV who are at risk of blood clots to receive drugs which will minimize the risks of developing these blood clots but at the moment the investigators are not sure which drugs will best control the disorder.

The purpose of this study is to look at the effectiveness of giving patients who have been diagnosed with ET and PV a study drug regimen using Aspirin and PEGASYS (also known as Pegylated interferon alfa-2a, instead of the standard treatment drug called Hydroxyurea (or hydroxycarbamide or Hydroxyurea), for whom this drug may not be suitable. The drug may not be suitable either because it is not adequately controlling the number of blood cells or some specific side effects occur.

Single Arm Salvage Therapy With Pegylated Interferon Alfa-2a for Patients With High Risk Polycythemia Vera or High Risk Essential Thrombocythemia Who Are Either Hydroxyurea Resistant or Intolerant or Have Had Abdominal Vein Thrombosis

Further study details as provided by Ronald Hoffman, Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:

Evaluate the ability of Pegylated Interferon Alfa-2a to achieve Complete Response or Partial Response in patients with (1) high risk polycythemia vera or (2) high risk essential thrombocythemia or (3) splanchnic vein thrombosis [ Time Frame: 4 years ]

Secondary Outcome Measures:

To evaluate the toxicity and tolerability of therapy Pegylated Interferon Alfa-2a in each of the 3 strata by recording the number of adverse events that occur during the study by using CTC 4.0 as the guide. [ Time Frame: 4 years ]

To measure the impact of Pegylated Interferon Alfa-2a on key biomarkers of the disease(s)by measuring the JAK2 allele burden. [ Time Frame: 4 years ]

Improvement in disease symptoms will be measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) instrument being used in this study.

To estimate survival, and incidence of development of myelodysplastic syndrome, myelofibrosis, or leukemic transformation during therapy Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]

We plan to capture the rate of disease progression to a more advanced myeloid malignancy.

Estimate the observed incidence of major cardiovascular events during therapy Pegylated Interferon Alfa-2a. [ Time Frame: 4 years ]

Capture and record the cardiovascular events that occur during the study.

To measure the impact of Pegylated Interferon Alfa-2a on JAK2-V617F, CALR, hematopoietic cell clonality in platelets and granulocytes in females, bone marrow histopathology, and cytogenetic abnormalities. [ Time Frame: 4 years ]

The impact of PEGASYS on JAK2 will be measured by the allele burden; hematopoietic cell clonality will be measured by whether patients with clonal disease return to polyclonal; bone marrow histopathology will be measured by going from abnormal to normal; cytogenetic abnormalities will be measured by seeing if the cytogenetics go from abnormal to normal.

If source documentation of diagnostic criterion #1 cannot be obtained, then diagnosis can be made with (1) the addition of an erythropoietin level below the reference range of normal AND (2) bone marrow biopsy showing hypercellularity for age with trilineage (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation.

Essential Thrombocythemia (all 6 criteria required)

Platelets count ≥ 450 x 10 to 9/L

Megakaryocyte proliferation with large and mature morphology. No or little granulocyte or erythroid proliferation. Patients may have up to and including 2+ marrow reticulin fibrosis.

Not meeting WHO criteria for CML, PV, MDS, PMF or over myeloid neoplasm

Demonstration of clonal cytogenetic marker or no evidence for a reactive thrombocytosis.

Absence of a leukoerythroblastic blood picture.

May participate in study without presence of JAK2V617F.

Patients must have high risk disease as defined below:

High risk PV ANY ONE of the following:

Age ≥ 60 years

Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related

Previous documented thrombosis, erythromelalgia or migraine (severe, recurrent, requiring medications, and felt to be secondary to the MPN) either after diagnosis or within 10 years before diagnosis and considered to be disease related

Presence of leg ulcers or other unacceptable Hydroxyurea-related non-hematological toxicities, such as unacceptable mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis or fever at any dose of Hydroxyurea.

Patients cannot have any other form of chemotherapy for their MPD (other than hydroxyurea). Specifically prior interferon or JAK2 inhibitors are prohibited.

If a patient has received prior hydroxyurea, they should be tapered off hydroxyurea over a period of the first 2 months of Pegylated interferon alfa-2a therapy. Taper is at the treating physician's discretion, but must be absent (completed) by the start of the third month.

Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)

Presence of any life-threatening co-morbidity

History of active substance or alcohol abuse within the last year

Any contraindications to pegylated or non-pegylated interferon

Subjects who have a positive pregnancy test, are pregnant, lactating or of reproductive potential and not practicing an effective means of contraception

History of psychiatric disorder (e.g. depression; suicidal ideation; psychosis) Subjects with a history of mild depression may be considered for entry into this study, provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable based on the investigator's normal practice for such subject.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01259817

Locations

United States, Arizona

Mayo Clinic

Scottsdale, Arizona, United States, 85259

United States, California

The Palo Alto Clinic

Palo Alto, California, United States, 94301

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20007

United States, Georgia

Emory Hospital

Atlanta, Georgia, United States, 30322

United States, Illinois

John H. Stroger Hospital of Cook County

Chicago, Illinois, United States, 60612

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

United States, Kansas

University of Kansas Cancer Center

Westwood, Kansas, United States, 66205

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, New York

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

Weill Cornell Medical College

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States, 27157

United States, Pennsylvania

Geisinger Cancer Center

Danville, Pennsylvania, United States, 17822

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Italy

Ospedale Riuniti de Bergamo

Bergamo, Italy

University Of Florence

Florence, Italy

Ospedale San Maartino Genova

Genova, Italy, 11632

San Matteo Hospital

Pavia, Italy, 27100

Universita Cattolica del Sacro Cuore

Rome, Italy

Sponsors and Collaborators

Ronald Hoffman

Myeloproliferative Disorders-Research Consortium

National Cancer Institute (NCI)

Roche Pharma AG

Investigators

Principal Investigator:

John Mascarenhas, MD

Icahn School of Medicine at Mount Sinai

Principal Investigator:

Ellen Ritchie, MD

Myeloproliferative Disorders-Research Consortium

Principal Investigator:

Alessandro Rambaldi, MD

Myeloproliferative Disorders-Research Consortium

More Information

Responsible Party:

Ronald Hoffman, Professor of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai